In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
Effective conduction of action potentials in the mammalian central nervous system (CNS) requires proper ensheathment and insulation of neuron axons by myelin. Impairments of oligodendrocyte cells, the myelinogenic cells of the mammalian CNS, cause a number of debilitating and often fatal human conditions. The incapacitating effects of myelin defects are typified by motor and sometimes cognitive deficiencies and are readily apparent in congenital dysmyelinating disorders as well as acquired demyelinating conditions such as multiple sclerosis and cerebral palsy. Treatment via remyelination necessitates either the restoration of the myelinating capacity of endogenous cells or transplantation of exogenous, myelinating cells.
Transplantation of fetal human glial progenitor cells has been shown to lead to recovery in a lethally hypomyelinated mouse model (Windrem, et al., Cell Stem Cell, 2(6):553-65 (2008). While clearly establishing proof-of-principle for translation to human patients, cells from aborted human fetuses not only face ethical and immunological challenges; however, providing the number of cells needed on a clinical scale currently is not realistic. Thus, a major limiting factor to the understanding and treatment of myelin-related neurodegenerative disorders is the lack of a scalable and tractable platform for the study of oligodendrocyte development and for screening of pharmaceuticals.
Stem cell biology has garnered much attention due to the potential to impact human health through disease modeling and cell replacement therapy. Pluripotent stem cells in particular theoretically offer an abundant source of glial cells and their progenitors. While previous studies have created excitement for myelin repair by clearly demonstrating that oligodendrocytes can be derived from pluripotent cells, results have yet to yield a system to study oligodendrocyte lineage that provides high cell population homogeneity without reliance on immunopanning, antibiotic resistance, or cell sorting techniques to improve population characteristics. The excitement for myelin repair has thus been tempered since pure populations of oligodendrocyte progenitor cells (OPCs) are difficult to obtain in clinically-relevant quantities. Methods for providing pure and plentiful glial cells are necessary to enable therapy through transplantation.
There is thus a need in the art for production of cells and cell populations of the glial lineages, and in particular for OPCs and oligodendrocytes. The present invention addresses this need.